Population-level interventions for the primary prevention of dementia: a complex evidence review

Summary Dementia risk reduction is a global public health priority. Existing primary prevention approaches have favored individual-level interventions, with a research and policy gap for population-level interventions. We conducted a complex, multi-stage, evidence review to identify empirical evidence on population-level interventions for each of the modifiable risk factors identified by the Lancet Commission on dementia (2020). Through a comprehensive series of targeted searches, we identified 4604 articles, of which 135 met our inclusion criteria. We synthesized evidence from multiple sources, including existing non-communicable disease prevention frameworks, and graded the consistency and comprehensiveness of evidence. We derived a population-level intervention framework for dementia risk reduction, containing 26 high- and moderate-confidence policy recommendations, supported by relevant information on effect sizes, sources of evidence, contextual information, and implementation guidance. This review provides policymakers with the evidence they need, in a useable format, to address this critical public health policy gap. Funding SW is funded by a 10.13039/501100000272National Institute for Health and Care Research (NIHR) Doctoral Fellowship. WW and LF are part funded by the 10.13039/501100000272NIHR Applied Research Collaboration East of England. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.


Introduction
With population ageing, dementia has emerged as a major public health challenge.Global prevalence is forecast to almost triple in the coming decades, to 150 million people living with dementia in 2050, mostly in low and middle income countries (LMICs). 1 In addition to the human cost to people with dementia and their families, dementia also places significant burden onto health and social care systems, as well as the broader economy, with global societal costs estimated as $1313.4 billion in 2019. 2 Evidence from high income countries suggests that dementia incidence can be reduced. 3,4Moreover, health behaviours such as eating a healthy diet, being physically active, and not smoking are associated with delaying onset of dementia by longer than the mortality benefit, meaning a 'compression of morbidity' and an associated reduction in disease costs. 5,6yntheses of observational studies by the Lancet commission on dementia has identified 12 potentially modifiable lifecourse risk factors for dementia, collectively associated with around 40% of dementia prevalence (higher in LMICs 7 ): low educational attainment, hearing loss, traumatic brain injury (TBI), hypertension, excess alcohol, obesity, tobacco smoking, depression, social isolation, physical inactivity, air pollution, and diabetes. 8Moving beyond observational data on risk factor associations, to interventional evidence measuring empirical effects on dementia prevalence is difficult because risk is accumulated across the lifecourse, pathology builds up over decades, and disease onset is often distal to cardiovascular events. 9ausality must therefore be considered on the balance of evidence.If causality is assumed, it is possible to focus the assessment of the evidence for dementia prevention policy on changes in the risk factors themselves, rather than empirically measuring changes in dementia prevalence itself.
Prevention of a disease by addressing its risk factors is known as 'primary prevention', which can be achieved by (i) 'individual-level interventions'which target individuals with high risk profiles and encourage or support them to adopt healthier behaviours or receive clinical interventions; and (ii) 'population-level interventions'which target the risk profile of the whole populations or communities by changing societal conditions. 10Population-level approaches have large potential effectiveness, economic, sustainability, and equity benefits over individual-level approaches, [9][10][11][12] but have been under-researched for dementia. 13,14he aim of this review is to summarize the best available evidence on which population-level interventions policymakers should consider adopting, to advance dementia prevention.It was not feasible to search the evidence bases of all 12 different risk factors through separate systematic reviews, and the production of a long, unfocused list of potentially effective interventions would be of limited utility to policymakers.Instead, we adopted a complex review approach 15 in which we synthesize the evidence pragmatically and synergistically, identifying intervention themes, key contextual considerations, and implementation guidance, across each of the evidence bases of the 12 risk factors, to produce a population-level dementia risk reduction framework to guide policymakers.

Review structure
The review was conducted in four stages: (i) review of general non-communicable disease (NCD) prevention reviews; (ii) identification of population-level interventions for 'typical NCD' risk factors; (iii) identification of population-level interventions for 'dementia-specific' risk factors; and (iv) synthesis and production of a populationlevel dementia risk reduction framework.More detail on each stage is provided below.

Review procedures
This review was registered on Prospero (ID: CRD42023396193).
All literature searches conducted in each review stage were developed and piloted with an expert medical librarian (IK).No language restrictions were applied.Full details of the search strategies are available in Appendix A.
In each of the review stages, article screening and selection was performed by two independent reviewers (SW and either LW or NM).Data extraction was by preagreed extraction template and was performed by SW and checked by LW.Reviewers (SW, NM and LW) met to discuss and resolve conflicts in selection and extraction at each review stage.
Throughout the review we considered populationlevel interventions to be: 'measures applied to populations, groups, areas, jurisdictions, or institutions with the aim of changing the social, cultural, physical, commercial, economic, environmental, occupational, or legislative conditions to make them less conducive to the development or maintenance of the modifiable lifecourse risk factors for dementia, and/or more conducive to the development or maintenance of the modifiable lifecourse protective factors for dementia. 16' (i) Review of general NCD prevention literature Significant efforts have already been undertaken to summarise the best interventions for the general prevention of NCDs. 17All of the 12 risk factors, as identified by the Lancet commission on dementia, 8 are either NCD risk factors (low formal education, hearing loss, TBI, alcohol, obesity, smoking, social isolation, physical inactivity, and air pollution) or NCDs in their own right (diabetes, hypertension, depression).However, we considered that the general NCD prevention literature would be more mature with respect to some risk factors compared to others.We therefore conducted a rapid umbrella review of noncommunicable disease prevention literature, to identify which risk factors were comprehensively included by this literature, and what types of population-level interventions were recommended.
On 12th of January 2023, and updated on 4th January 2024, we searched Medline via Ovid, Scopus, Web of Science, the Cochrane Library, and publications from the World Health Organization (WHO), and the UK National Institute for Health and Care Excellence (NICE), using terms for NCD, prevention, and review (Appendix A).We included reviews that were informed by systematic literature searches.In order to capture the generic NCD prevention literature, we excluded reviews that did not aim to summarise the totality of, or a significant proportion of, the NCD prevention literature (i.e., we excluded reviews with a narrow focus on a single disease).We excluded reviews in which none of the included interventional evidence met our definition of a population-level intervention.To capture an up-todate reflection of the evidence base, we excluded reviews published more than a decade ago.
We assessed the risk of bias in the included reviews using the 'A MeaSurement Tool to Assess systematic Reviews 2' (AMSTAR 2) tool. 18We extracted data on risk factor(s) and/or disease(s) included, relative focus on population-level interventions, and types of populationlevel interventions considered to be effective.

(ii) Identification of interventions for typical NCD risk factors
Stage (i) identified six 'typical NCD' risk factors: smoking, alcohol, physical inactivity, obesity, hypertension, and diabetes (i.e., those that were consistently and comprehensively covered by existing NCD prevention literature; see Results section for more details), but the included reviews generally scored poorly on quality assessment and lacked detail on the interventions.We therefore conducted a focused search, on 22nd March 2023, for high-quality evidence summarising population-level interventions to address these six risk factors, drawing from two authoritative sources for the curation and weighing up of evidence to inform policy: the Cochrane Library, and the WHO.We searched the Cochrane library for reviews on any of the six typical NCD risk factors (Appendix A).For the WHO, we extracted data from Appendix 3 of the WHO's Global Action Plan for the Prevention and Control of NCDs, 19 which summarizes the interventions considered in cost-effectiveness modelling by WHO for inclusion in the 'Best Buys' 17 report.This in turn draws interventions from regularly updated technical briefs for each of four risk factors (tobacco, smoking, alcohol, diet) and key diseases (including diabetes, and hypertension).
We included articles that summarised empirical estimates of the effects of population-level interventions for the prevention or control of any of the six typical NCD risk factors (we included calorie and sugar consumption as empirical outcomes for diet/obesity policy).We extracted description, study design, and findings (quantitative estimates of risk factor reduction) of the population-level intervention(s), assessments of the strength of evidence, and contextual information including study populations, equity effects, and implementation guidance.

(iii) Identification of interventions for dementia-specific risk factors
In order to summarize the evidence for population-level interventions to address the remaining six risk factors (education, hearing loss, TBI, depression, social isolation, and air pollution), in June 2023 we searched for publications in the Cochrane library, and from the WHO website using terms related to each of the risk factors.We also extracted any relevant data from the literature associated with appendix 3 of the WHO Global Action Plan.For depression and social isolation, we additionally searched the Campbell Collaboration library.
Although these searches identified relevant literature for all six dementia-specific risk factors, they yielded no suitable recommendations for three risk factors (education, depression, and social isolation).We therefore undertook further, more targeted, searches for these risk factors, designed to identify high-quality research which may have been excluded by the databases above.We searched the Turning Research into Practice (TRIP) database, Google Scholar, and via consultation with field experts.We consulted the types of interventions identified in stage (ii) to hypothesise similar interventions, which may be applicable to these three risk factors.The hypothesised interventions were used to structure the targeted searches (Appendix A).
Article inclusion, and data extraction, followed the same procedures as stage (ii).

(iv) Synthesis and derivation of a population-level intervention framework
Three authors (SW, LW and NM) met to apply confidence grades (low, medium, high) for the various interventions identified through stages (i) to (iii), according to the criteria in Box 1 which were developed specifically for this review.Owing to the nature of the interventions evaluated in the included articles, we considered evidence from a range of interventional and natural experiment study designs, and the inherent strengths and weaknesses of these designs were considered when appraising the strength of evidence.
The recommended interventions were then compared against example NCD prevention frameworks identified in stages (i), (ii) or through professional networks, to identify intervention types which accurately grouped our recommendations, and to structure our own framework.
We then derived a 'population-level dementia risk reduction intervention framework', with columns grouping intervention types, rows listing risk factors, and populated only with recommendations judged at moderate or high confidence.To aid the use of the framework by policymakers, further relevant information was summarised, including example effect sizes, sources of evidence, key contextual information, whether evidence came from high-income countries (HIC) or LMICs, and implementation guidance.When selecting effect sizes to report, we used point estimates from meta-analyses where these were available, or the most conservative estimate from the highest-quality review or primary study, where meta-analysis was not available.

Role of funding
The funders played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

High confidence recommendations
Interventions with comprehensive, consistent, and robust evidence, across a range of contexts, of a beneficial causal effect on the prevalence a risk factor Moderate confidence recommendations Interventions with clear and robust evidence of a beneficial causal effect on the prevalence of a risk factor, but only in a limited number of contexts Low confidence recommendations Interventions with empirical evidence demonstrating a clear signal that the intervention can reduce prevalence of a risk factor, but for which the evidence base lacks consistency or comprehensiveness We first describe the findings of each stage of the review, and then outline the findings for each risk factor in turn.

(i) Review of general NCD prevention literature
Stage (i) of the review identified ten reviews (Fig. 1), of which nine were rated as being of 'critically low' quality, and one was rated as 'low' (Supplementary Table 1A).As such we were unable to rely heavily on the recommendations in these reviews, several of which were scoping-type documents owing to their broad view of the NCD prevention literature.Instead, we used their findings (Supplementary Table 1B) as supportive evidence for the interpretation of evidence found in later review stages.In addition, we identified that the evidence base would be most mature for six risk factors: tobacco smoking, excess alcohol, physical inactivity, obesity (which would often be considered through a lens of poor diet, from a primary prevention perspective), hypertension, and diabeteswhich together we considered as 'typical NCD risk factors'; and that more specific searches would likely be needed for the remaining six risk factors (hereafter named the 'dementia-specific' risk factors).
The WHO's Global Action Plan for the prevention and control of NCDs was published in 2013.Appendix 3 of this report detailed key recommended interventions for four risk factors (smoking, alcohol, poor diet, physical inactivity) and four diseases (including cardiovascular disease, with some direct relevance to hypertension).The Appendix 3 document was then updated in 2017, in order to produce the 'Best buys and other recommended interventions for the prevention and control of NCDs' report.The WHO are currently in the process of updating the appendix 3 document for a second time, with the most recent draft published in August 2022.We extracted the 2013, 2017, and 2022 versions of appendix 3, along with the most recently updated technical annex (December 2022), and the latest accompanying technical briefs for each risk factor and for cardiovascular disease (November 2022) (Supplementary Table 2B).
The targeted searches yielded further results for depression (n = 16), social isolation (n = 19), and education (n = 17) (Fig. 1), and the extracted intervention data is reported in Supplementary Table 3B-D, respectively.

(iv) Synthesis and derivation of a population-level intervention framework
Table 1 shows the grading of evidence for each recommendation, by risk factor.In total, we identified 11 highconfidence recommendations, 15 moderate-confidence recommendations, and 11 low-confidence recommendations, covering 10 of the risk factors (with no recommendations for diabetes or social isolation).
Across the review, and through professional networks, we identified nine existing population-level intervention frameworks, for NCDs in general (n = 3), diet and/or obesity (n = 4), and alcohol (n = 2) (Supplementary Table 4).Comparing the intervention types described by these frameworks, with the high-and moderate-confidence recommendations from our review, we considered four intervention types for our framework: fiscal interventions (changing the affordability of healthy and unhealthy products/behaviours), marketing and/or advertising interventions (changing the way the population are exposed to healthy and unhealthy products), availability interventions (changing the population's access to healthy and unhealthy products/behaviours), and legislative interventions (changing the law to mandate certain behaviours from industry or the population).
Table 2 shows the derived population-level dementia risk reduction intervention framework, populated by interventions with high-and moderate-confidence.We identified most interventions of the availability type (n = 8) and legislative type (n = 8), followed by fiscal (n = 5) and marketing/advertising (n = 5).
For 13 of the recommendations we found supporting evidence from both HIC and LMICs, for 10 we found evidence from HICs only, and for three we found evidence from LMICs only (Table 2).
We did not identify any high-or moderateconfidence recommendations for diabetes, depression or social isolation.
Table 3 reports key information for policymakers regarding each recommendation, including example effect sizes, evidence sources, contextual considerations, and implementation guidance.

Findings by risk factor Tobacco smoking
Consistent evidence, from across several reviews, demonstrates the effectiveness of increasing excise taxes, smoking bans in public places, and comprehensive marketing bans and packaging controls.In particular, taxation policies and smoking bans, are supported by evidence from both HIC and LMICs.
The WHO also recommends introduction of a minimum legal age for smoking, which aims to delay the age of smoking initiation.However, we only identified supporting empirical evidence from a 2005 Cochrane review (Supplementary Table 2A) focussed on interventions to improve enforcement of this legislation (not the direct empirical effect of the legislation itself), so we have graded this as a low-confidence recommendation.

Excess alcohol
Consistent evidence demonstrated the effectiveness of excise taxes and minimum unit prices for alcohol, and we recommend these with high-confidence.Empirical data for the newer policy measure, minimum unit pricing, was only reported from HICs.
There was also clear evidence for comprehensive marketing bans, and from LMICs for interventions to restrict the physical availability of alcohol, for example, through limiting the permitted hours of sale, or reducing the density of licensed alcohol vendors.

Obesity
Consistent evidence, from several reviews, demonstrates the effectiveness of interventions targeting diet to reduce obesity, specifically increasing taxation of unhealthy products such as sugar-sweetened beverages, reducing portion/package sizes, and reformulation policies to reduce the sugar content of available foodssupported by consistent evidence that mandatory policies are more effective than industry-led voluntary policies.
We found clear evidence for food procurement policies, e.g., improving the healthiness of food available in schools or hospitals, and for marketing policies to restrict advertising of unhealthy foods to children, and menu labelling in restaurantsthough these evidence bases are still developing.
Evidence for front of food pack labelling is mixed, and equitable population-level effects are only likely to be achieved if they lead to reformulation of productswe grade this as a low-confidence recommendation.We also grade subsidies of healthy foods as a lowconfidence recommendation because, although the evidence base was consistent and these intervention could clearly be an important part of a whole-system approach to obesity prevention, the only reported outcomes were improvements to healthy food intake, and not other important proxies for obesity such as total calorie intake.

Physical inactivity
The evidence base for physical inactivity is relatively less mature than for smoking, alcohol, or poor diet.We Campbell collaboration review reported direct evidence from 7 studies (free primary schools in Uganda n = 3 studies, studies of primary school tuition waivers (e.g., via conditional payments to the school) n = 3 from Haiti, Pakistan, Ecuador, and secondary school tuition waivers n = 1 from Ghana, supported by 10 further studies which were multi-component but included free schooling) Moderate (E2) Provide free lunches in primary schools, where a lack of adequate food would otherwise be a barrier to school attendance Campbell collaboration review reported two studies reported effects on boys and girls combined.One examined the effects of policies to improve access and quality of schooling in Burkina Faso, using secondary data from surveys and RCTs, reporting significant benefits, mainly for in-school feeding programmes and also out of school rations in some cases.
Another considered the effect of a national policy to provide free lunches to all primary school children in India and reported significant benefits to primary school enrolment.make one moderate-confidence recommendation, for urban and transport design and planning policies, which collectively have a clear evidence base showing that making the built environment and infrastructure more amenable to physical activity, including active commuting, can reduce physical inactivity.We find mixed evidence, and make a low-confidence recommendation, for interventions specifically targeted at schools or workplaces, though these are clearly important components for any whole-of-community approach to reducing physical inactivity (for example, transport policies to increase cycling to work will benefit from adequate workplace cycle racks and shower facilities).

Hypertension
Based on the evidence we appraised, we make two recommendations specifically for hypertension; however, the evidence base for both reformulation (high-confidence) and public food procurement (moderate-confidence) interventions comes from a mix of studies considering sodium content specifically, including two Cochrane reviews (Supplementary Table 2A), and others which consider dietary sodium interventions as part of broader dietary policy (Supplementary Table 2B).

Diabetes
We make no specific recommendations for populationlevel interventions with empirical evidence showing a reduction in diabetes.However, obesity and physical inactivity are established risk factors for type II diabetes (T2DM), and we can therefore expect the interventions for obesity and physical inactivity to convey indirect dementia risk reduction benefits through a reduction in T2DM prevalence.

Depression
We did not make any high-or moderate-confidence recommendations for population-level interventions to reduce depression, despite identifying several highquality reviews, including Cochrane reviews, which had looked directly for relevant evidence.The evidence base suffers from limitations around outcome ascertainment, with many studies considering 'depressive symptoms' measured by a single-question on a survey, rather than comprehensive clinical assessment.
We found mixed results for interventions aiming to improve social determinants of health (SDOH), such as social security interventions, housing interventions, and direct cash transfers (Supplementary Table 3A and B)with some evidence that these interventions can reduce depression, but the evidence base was inconsistent and it was not clear which factors drive a successful, rather than null, outcome.We therefore grade this as a lowconfidence recommendation.Through professional networks we identified one study, too recent to be included in any review articles, that demonstrated a reduction in anti-depressant prescribing (objectively, using electronic health records) in a deprived area of the UK.The intervention was the introduction of a community wealth building (CWB) programme which involved working with local anchor institutions to address upstream economic inequalities through measures like equitable distribution of investments and procurement, and commitment to paying a 'living wage' to all employees. 20

Social isolation
We did not make any recommendations for populationlevel interventions to reduce social isolationdespite identifying several recent systematic reviews, including some that specifically searched for evidence on population-level interventions.

Traumatic brain injury
Clear evidence demonstrates the effectiveness of legislation to mandate the use of bicycle helmets for children, and motorcycle helmets for passengers of all ages, in reducing TBI.Further evidence, from HICs, suggested that provision of bicycle helmets to children from low socioeconomic backgrounds, school-based and community-based programmes to encourage helmet use, and proper enforcement of the legislation, will increase the likelihood of success of these recommendations.
More broadly, there is clear evidence, summarised through a series of articles from WHO, for road safety interventions to reduce the incidence of road traffic injuries (of which head injuries will constitute a proportion), these include speed management, segregated off-road cycle lanes, seatbelt legislation, and drink driving legislation (Supplementary Table 3A).

Low educational attainment
A Campbell Collaboration review reports robust evidence, particularly from Sub-Saharan Africa, for the removal of financial and food barriers from school (predominantly primary school) attendance.These include national policy to remove school fees, household cash transfers conditional on school attendance, and provision of free school lunches with/without take home rations (Supplementary Table 3D).
Several reviews identify empirical evidence from Europe that raising the mandated school leavers age (post-intervention leaving age ranged between 14 and 18 years in the included studies) increases the total amount of education received by the population, provided there is sufficient capacity within the education system.
Several of the studies reported equity impacts of these three recommendations, with children from lower income households standing to gain the most.

Air pollution
We make two recommendations for ambient air pollution, with clear evidence demonstrating a reduction in pollutants such as particulate matter (PM2.5 and PM10) and carbon monoxide (CO) from urban traffic restrictions, such as low emission zones, and postponement of non-essential polluting activities, such as road cleaning, on high-pollution days.
We make one recommendation for indoor air pollution, with consistent evidence from a WHO systematic review reporting empirical reductions in PM2.5 and CO resulting from stove exchange programmes that replaced traditional cookers using biomass with newer devices using cleaner fuels.A second review by WHO also reported key contextual factors to consider when implementing this type of intervention, including the provision of stove maintenance where required, and ensuring traditional foods can be cooked effectively on the newer stoves (Table 3).

Hearing impairment
We found clear evidence that occupational interventions involving exchanging equipment for quieter alternatives, and provision of (and mandated use of) hearing protective devices for those working in consistently noisy environments can reduce hearing loss (Supplementary Table 3A).
No evidence was found for policy interventions to make hearing corrective devices more readily available or affordable to the general public.

Discussion
We identified clear and robust evidence for the effectiveness of 26 population-level interventions to reduce the prevalence of nine of the 12 risk factors, of which 23 have been empirically evaluated in HICs, and 16 in LMICs.We identify interventions that act through fiscal (e.g., removing primary school fees), marketing/advertising (e.g., plain packaging of tobacco products), availability (e.g., cleaner fuel replacement programmes for cooking stoves), and legislative (e.g., mandated provision of hearing protective equipment at noisy workplaces) levers.
The evidence base was more mature with regards to some risk factors, and some intervention types, than others.We were unable to include any recommendations in our framework for diabetes (directly), depression or social isolation.For depression, we did identify a developing evidence base for SDOH-type interventions such as community wealth building, social welfare policies, and housing improvements, however, the evidence base was not yet strong enough for inclusion in our framework.For social isolation, we identified several recent systematic reviews that have specifically looked for evidence on population-level interventions, for example urban green space interventions, and found a paucity of high-quality evidence.Given the importance of depression and social isolation in their own right, as well as being modifiable risk factors for dementia, these represent significant evidence gaps.
The evidence bases for the fiscal, legislative, and availability intervention types were relatively more mature than for marketing and advertising restrictions.However, we note this is an increasing area of research, 21 and the quality of evidence may be expected to improve in the near future.
As outlined in the introduction, primary prevention can be characterised through a binary distinction between individual-level and population-level approaches.
However, it is significant to note that our review of existing NCD prevention frameworks (Supplementary Table 4) identified one framework in particular 22 that conceptualised the types of interventions included in this review as an intermediate level between superficial, individual-level interventions, and more radical, societallevel change.This speaks to an intractable trade-off between the relative ease of implementation and evaluation of an intervention, and the profoundness of the scale of change that can be achieved.To take obesity as an example, appetite-suppressant drugs are readily amenable to clinical trials to demonstrate efficacy, but depend on healthcare access and drug affordability, and do not address the root causes of obesity, so will have limited impact on obesity prevalence and will increase health inequalities.At the other end of the spectrum, making significant, sustained (without the need for ongoing intervention) changes to the food system, such that healthier products are more available, affordable, and socially desirable than unhealthy alternatives, is difficult to achieve, and even more difficult to evaluate directly through changes to individuals' body mass index.In this context, the population-level interventions identified by this review (e.g., taxation on sugarsweetened beverages) can be seen as a pragmatic middle-ground, enabling policymakers to achieve meaningful, and equitable, reductions in population dementia risk, with support from empirical evidence of effectiveness.
Our complex evidence review approach enabled us to identify evidence on the best-researched populationlevel interventions, across 12 different risk factors, identifying evidence relevant to all levels of government, in both HICs and LMICs.This approach assumed causality of the risk factors on dementia, and none of the included articles measured a change in dementia prevalence directly.In addition, for obesity, we assumed that measured reductions in total caloric or free sugar intake would reduce weight.Due to the complexity and late-life nature of the dementia syndrome, proving beyond doubt the causality of a dementia risk factor is challenging.The evidence bases of the 12 risk factors we included have been adjudged by the Lancet's commission of experts to be sufficiently robust to consider them as potentially modifiable risk factors.In addition to the potential dementia risk reduction benefit, each of these risk factors also represent valid targets for public health policy in their own right.
By incorporating evidence from existing NCD prevention reviews and frameworks, we were able to meaningfully synthesise this evidence into a userfriendly framework, which can help to structure policymaking approaches to population-level dementia risk reduction.Given the breadth of our research question, it was not feasible to conduct a systematic review of primary evidence, and pilot searches confirmed that even an umbrella review would have produced an unmanageable number of potential studies.Moreover, a systematic review aims to identify all literature on a topic, whereas policymakers (and the professionals who work with them) really want to know what the bestevidenced interventions are, and how to implement them 15,23 we designed our study accordingly.Our approach may have missed some relevant interventions, particularly those from emerging evidence bases which may not be well covered by secondary data sources like Cochrane and WHO yet.For example, research since the Lancet commission's 2020 report has suggested strengthening evidence of a causal link between repeated sports-related concussions (mild TBI) and dementia risk 24 and some policy-level interventions such as rule changes to minimise collisions have been identified. 25,26It will be relevant to periodically update our review to capture these emerging evidence bases.
We included key contextual information for each policy recommendation (Table 3) but we did not explicitly consider negative effects of the policy recommendations, such as higher tax burden or reduced autonomy.We only include recommendations in our framework that were judged to be high-or moderateconfidence.These criteria are clear and were developed specifically for this review, and gradings for each recommendation were agreed between three co-authors (SW, LW, NM), nevertheless there is some subjectivity in these judgements.
Whilst it is easy to conceptually distinguish population-level interventions from individual-level ones, in practice there are interventions that blur this boundary, and definition of 'population-level interventions' vary. 27We focused our population-level intervention definition on interventions that change societal conditions, leading to the exclusion of some interventions, such as screening, vaccination, and mass media interventions, which are delivered at scale, but are clinical or high-agency in their mechanism.This approach ensured that all our recommendations are likely to achieve the key advantages of the population-level approach as described by Geoffrey Rose 10 : magnitude, equity, and longevity of benefit. 12The recommended interventions will typically benefit the population across the lifecourse (e.g., reduction of pollution benefits everyone from children to older people), however, as evidence strengthens that specific lifecourse phases are important for dementia risk accumulation, targeting of some interventions towards specific population subgroups may be possible.
We included only interventions for which there were empirical data on showing beneficial changes in risk factors for dementia.Study designs included randomized control trials, quasi-experimental studies, and natural experiment designs.Due to the complex nature of population-level interventions, it was rarely feasible for studies to eliminate all possible sources of bias.The limitations of the included studies were considered when grading evidence.Forms of evidence beyond these designs are clearly important to a comprehensive understanding of disease and prevention strategies, including observational, qualitative, and modelling data.However, there are potentially unknowable factors when applying these non-empirical data to policy implementation, and direct interventional evidence holds a tangible advantage when communicating with policymakers, which drove our decision to prioritize this evidence.Where relevant, we considered the supporting evidence from other types of data, and this is described explicitly in the evidence tables.And we provide policymakers with key implementation guidance and contextual information for the recommendations, in Table 3.
Policymakers, public health leaders, and dementia researchers aiming to reduce dementia are presented with two broad approaches, identification of high-risk individuals and encourage them to adopt healthier lifestyles and/or take up clinical interventions (individuallevel approaches), or the introduction of policies and interventions that make societal conditions less conducive to the development of dementia (population-level approaches).Population-level approaches have the greatest reach and can achieve the largest, sustained, and equitable reductions in disease.Nevertheless, individual-level approaches have dominated policy and research spheres because they are considered easier to implement and evaluate. 11,14In this review, we have made 26 recommendations for interventions with strong empirical evidence that they can reduce dementia risk factors across the population.In addition, we provide key accompanying information and resources that policymakers can use to implement these recommendations in their own context.Whilst more research is needed, in particular concerning population-level interventions to reduce depression and social isolation, the central message of this review is that we already have enough evidence to tackle a major global public health challenge.The policies and interventions recommended have relevance at all levels of government, in both HIC and LMICsthe time for policy action is now.

Outstanding questions
• Identification of effective population-level interventions to reduce depression and social isolation.• Further causal epidemiology work to develop the evidence base for, and identify new, modifiable risk factors for dementia.• Interventional evidence and natural experiment studies to examine the effect of population-level interventions to reduce these risk factors on directly measured dementia incidence, where feasible.

Fig. 1 :
Fig. 1: Modified PRISMA flowchart showing article identification and selection, by review stage.OVID = Interface for accessing Medline.WoS = Web of Science.NICE = National Institute of Health and Care Excellence.WHO = World Health Organization.Cochr = Cochrane Library.Camp = Campbell Collaboration.Google = Google Scholar.TRIP = Turning Research Into Practice.E/PNs = Experts and Professional Networks.

Table 1 :
Grading of evidence.
ModerateHICs = High income countries.LMICs = Low-and middle-income countries.WHO = World Health Organization.RCT = Randomised Controlled Trials.FOPL = Front of pack labelling.PM = Particulate matter.CO = Carbon monoxide.NO = Nitrous Oxide.b TBI = Traumatic brain injury.HICs = High income countries a Supporting evidence for this recommendation includes data from both high and low/middle income countries.b Supporting evidence for this recommendation includes data from high income countries only.c Supporting evidence for this recommendation includes data from low/middle income countries only.

Table 2 :
Population-level dementia risk reduction framework.
NO2 = nitrous oxide.OR = odds ratios.N.B. "credible ranges" are quoted from the source literature by Levy et al., and are defined as "credible ranges for effect sizes based on the number of studies conducted, variation in results, and strength of evidence."

Table 3 :
Supporting information for the framework interventions.